ArticleOncogenesis2019
PPP2R2A prostate cancer haploinsufficiency is associated with worse prognosis and a high vulnerability to B55α/PP2A reconstitution that triggers centrosome destabilization.
Article in Oncogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- PARP Inhibition in Prostate Cancer With Homologous Recombination Repair Alterations.JCO precision oncology · 2021Pooled it
- PARP Inhibitor Sensitivity in Tumors Harboring Non-BRCA Homologous Recombination Gene Alterations: Current Evidence Across Ovarian, Breast, Prostate, and Pancreatic Cancers.International journal of molecular sciences · 2026Review
- Characterization of RNF144B and PPP2R2A identified by a novel approach using TCGA data in ovarian cancer.Scientific reports · 2025Article
- Article
- PP2A B55α inhibits epithelial-mesenchymal transition via regulation of Slug expression in non-small cell lung cancer.Cancer letters · 2024Article
- PP2A-B55 phosphatase counteracts Ki-67-dependent chromosome individualization during mitosis.Cell reports · 2024Article
- Non-coding RNA transcripts, incredible modulators of cisplatin chemo-resistance in bladder cancer through operating a broad spectrum of cellular processes and signaling mechanism.Non-coding RNA research · 2024Review
- Precision Medicine in Castration-Resistant Prostate Cancer: Advances, Challenges, and the Landscape of PARPi Therapy-A Narrative Review.International journal of molecular sciences · 2024Review
- Altering phosphorylation in cancer through PP2A modifiers.Cancer cell international · 2024Review
- LowTheranostics · 2024Article
- A Small Molecule Inhibitor of Leucine Carboxyl Methyltransferase-1 Inhibits Cancer Cell Survival.Frontiers in drug discovery · 2024Article
- Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance.Nature communications · 2023Article
- PP2A methylesterase PME-1 suppresses anoikis and is associated with therapy relapse of PTEN-deficient prostate cancers.Molecular oncology · 2023Article
- VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU.Cell death & disease · 2023Article
- Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules.The Journal of biological chemistry · 2022Review
- Expanding the prostate cancer cell line repertoire with ACRJ-PC28, an AR-negative neuroendocrine cell line derived from an African-Caribbean patient.Cancer research communications · 2022Article
- PP2A promotes apoptosis and facilitates docetaxel sensitivity via the PP2A/p-eIF4B/XIAP signaling pathway in prostate cancer.Oncology letters · 2022Article
- Genomic analyses of the metastasis-derived prostate cancer cell lines LNCaP, VCaP, and PC3-AR.The Prostate · 2022Article
- Article
- Immortalization of human primary prostate epithelial cells via CRISPR inactivation of the CDKN2A locus and expression of telomerase.Prostate cancer and prostatic diseases · 2021Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The PPP2R2A gene encodes the B55α regulatory subunit of PP2A. Here, we report that PPP2R2A is hemizygously lost in ~42% of prostate adenocarcinomas, correlating with reduced expression, poorer prognosis, and an increased incidence of hemizygous loss (>75%) in metastatic disease. Of note, PPP2R2A homozygous loss is less common (5%) and not increased at later tumor stages. Reduced expression of B55α is also seen in prostate tumor tissue and cell lines. Consistent with the possibility that complete loss of PPP2R2A is detrimental in prostate tumors, PPP2R2A deletion in cells with reduced but present B55α reduces cell proliferation by slowing progression through the cell cycle. Remarkably, B55α-low cells also appear addicted to lower B55α expression, as even moderate increases in B55α expression are toxic. Reconstitution of B55α expression in prostate cancer (PCa) cell lines with low B55α expression reduces proliferation, inhibits transformation and blocks xenograft tumorigenicity. Mechanistically, we show B55α reconstitution reduces phosphorylation of proteins essential for centrosomal maintenance, and induces centrosome collapse and chromosome segregation failure; a first reported link between B55α/PP2A and the vertebrate centrosome. These effects are dependent on a prolonged metaphase/anaphase checkpoint and are lethal to PCa cells addicted to low levels of B55α. Thus, we propose the reduction in B55α levels associated with hemizygous loss is necessary for centrosomal integrity in PCa cells, leading to selective lethality of B55α reconstitution. Such a vulnerability could be targeted therapeutically in the large pool of patients with hemizygous PPP2R2A deletions, using pharmacologic approaches that enhance PP2A/B55α activity.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.